Control of membrane-attached biofilms using surfactants

The effect of surfactants on membrane-attached biofilms (MABs) was studied in a lab-scale extractive membrane bioreactor (EMB). Twenty-two surfactants were screened for their potential of increasing the cell wall negative charge (i.e. the electrostatic repulsion between bacteria) of Burkholderia sp. JS150 bacterial strain. Surfactants resulting in increased bacterial negative charge were further investigated for their effects on MAB population morphology and MAB attachment behaviour. Microscopic investigation of the bacterial population in MABs showed that surfactants affect the development of flagella, suggesting changes in the attachment capability of the JS150 strain in the presence of different surfactants. Among the screened surfactants, teepol showed the best characteristics in relation to the reduction of MAB accumulation, and it was tested in an EMB system for the extraction of monochlorobenzene from a synthetic wastewater. Comparison with a control EMB, operated without surfactants under the same conditions, proved that teepol effectively reduces MAB accumulation on the membrane walls. As a result, the overall mass transfer coefficient in the presence of teepol was 53% higher than in the control EMB.     

Interpersonal violence in prehistoric San Pedro de Atacama, Chile: behavioral implications of environmental stress

The prehistoric population of San Pedro de Atacama lived through periods marked by prosperity and interregional interaction, as well as times of severe drought, social stress, and widespread poverty. A sample of 682 crania was analyzed for evidence of cranial trauma in order to assess changing patterns of interpersonal violence during the occupation of the oasis. It was hypothesized that the level of traumatic injuries in this population would parallel some of the changes seen in the archaeological record. Low fracture rates would be expected in periods of affluence and environmental stability, while periods characterized by environmental extremes and state collapse would yield elevated rates of aggression. This analysis found that rates of trauma escalated from 5.1% (5/99) in the earliest period, to 10.9% (10/92) in the Middle Horizon (AD 600-950). Although it may reflect problems related to increasing population density in the oasis, this increase is surprising, given that the early period witnessed the shift to permanent settlements, and the middle period was one of prosperity and plentiful resource availability. Trauma rates peaked at 35.6% (16/45) in an early Late Intermediate period (AD 950-1400) cemetery, with other Late Intermediate cemeteries demonstrating similarly high rates of traumatic injury. The elevated trauma rates during this period correlate with major droughts, the concentration of settlements on the oasis' east side, fortified structures, and material poverty, all reflected in the archaeological record. As the Late Intermediate waned and environmental conditions improved, trauma concomitantly decreased (7.0%), and remained low throughout the Inka occupation (AD 1400-1532). This indicates that while the Atacama was not peaceful, violence became commonplace only during periods of great social change and resource stress.     

Therapeutic efficacy of ipilimumab,an anti-CTLA-4 monoclonal antibody,in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases

The management of unresectable metastatic melanoma is a major clinical challenge because of the lack of reliably effective systemic therapies. Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has recently been proposed as a strategy to enhance cell-mediated immune responses to cancer, and clinical trials have demonstrated that anti-CTLA-4 therapy can produce durable outcomes with different response patterns than cytotoxic chemotherapy. We enrolled eight out of 155 patients with advanced melanoma in a multicentre phase II trial that evaluated the activity and tolerability of ipilimumab, a fully human, anti-CTLA-4 monoclonal antibody (; NCT00289627; CA184-008). Here we report our experience with three of these patients, who experienced progressive disease after a variety of previous therapies, including prior immunotherapies, and who achieved good outcomes with ipilimumab. One patient had a partial response ongoing at 17+ months on ipilimumab despite failure with four prior therapies, and the other two patients showed durable stable disease, both still ongoing at 17+ and 20+ months, respectively. The patient achieving a partial response experienced no side effects while receiving ipilimumab. The other two patients developed immune-related adverse events (irAEs) including rash (one case; grade 2) and diarrhoea (both cases; grades 1 and 2, respectively); the histopathology of colon biopsy samples from both was suggestive of colitis, with an abundant CD8+ T-cell infiltrate. Nausea, vomiting and acute pancreatitis were also observed in one patient. In addition, immunohistochemical findings of a dense CD8+, TIA1+ and granzyme B+ lymphoid infiltrate within a biopsied lesion provide indirect evidence of functional T-cell activation induced by treatment. These case reports highlight the potential for anti-CTLA-4-based therapy in previously treated patients with advanced melanoma. Moreover, because the patterns of response to ipilimumab differ from chemotherapy, we need to understand how and when patients may respond to treatment so that appropriate clinical decisions can be made.     

Ancient Leishmaniasis in a Highland Desert of Northern Chile

Background

Leishmaniasis is an infectious disease endemic today in many areas of South America.

Methodology

We discovered morphologic and molecular evidence of ancient infections in 4 female skulls in the archaeological cemetery of Coyo Oriente, in the desert of San Pedro de Atacama, Northern Chile. The boney facial lesions visible in the skulls could have been caused by a number of chronic infections including chronic Leishmaniasis. This diagnosis was confirmed using PCR-sequenced analyses of bone fragments from the skulls of the affected individuals.Leishmaniasis is not normally found in the high-altitude desert of Northern Chile; where the harsh climate does not allow the parasite to complete its life cycle. The presence of Leishmaniasis in ancient skulls from the region implies infection by the protozoan in an endemic area–likely, in our subjects, to have been the lowlands of North-Eastern Argentina or in Southern Bolivia.

Conclusions

We propose that the presence of the disease in ancient times in the high altitude desert of San Pedro de Atacama is the result of an exogamic system of patrilocal marriages, where women from different cultures followed their husbands to their ancestral homes, allowing immigrant women, infected early in life, to be incorporated in the Atacama desert society before they became disfigured by the disease. The present globalization of goods and services and the extraordinary facile movement of people across borders and continents have lead to a resurgence of infectious diseases and re-emergence of infections such as Leishmaniasis. We show here that such factors were already present millennia ago, shaping demographic trends and the epidemiology of infections just as they do today.     

Intrathecal NGF Administration Reduces Reactive Astrocytosis and Changes Neurotrophin Receptors Expression Pattern in a Rat Model of Neuropathic Pain

Nerve growth factor (NGF), an essential peptide for sensory neurons, seems to have opposite effects when administered peripherally or directly to the central nervous system. We investigated the effects of 7-days intrathecal (i.t.) infusion of NGF on neuronal and glial spinal markers relevant to neuropathic behavior induced by chronic constriction injury (CCI) of the sciatic nerve. Allodynic and hyperalgesic behaviors were investigated by Von Frey and thermal Plantar tests, respectively. NGF-treated animals showed reduced allodynia and thermal hyperalgesia, compared to control animals. We evaluated on lumbar spinal cord the expression of microglial (ED-1), astrocytic (GFAP and S-100β), and C- and Aδ-fibers (SubP, IB-4 and Cb) markers. I.t. NGF treatment reduced reactive astrocytosis and the density of SubP, IB4 and Cb positive fibers in the dorsal horn of injured animals. Morphometric parameters of proximal sciatic nerve stump fibers and cells in DRG were also analyzed in CCI rats: myelin thickness was reduced and DRG neurons and satellite cells appeared hypertrophic. I.t. NGF treatment showed a beneficial effect in reversing these molecular and morphological alterations. Finally, we analyzed by immunohistochemistry the expression pattern of neurotrophin receptors TrkA, pTrkA, TrkB and p75^NTR. Substantial alterations in neurotrophin receptors expression were observed in the spinal cord of CCI and NGF-treated animals. Our results indicate that i.t. NGF administration reverses the neuro-glial morphomolecular changes occurring in neuropathic animals paralleled by alterations in neurotrophin receptors ratio, and suggest that NGF is effective in restoring homeostatic conditions in the spinal cord and maintaining analgesia in neuropathic pain.     

Anaerobic bacteria infection in cystic fibrosis airway disease

Depletion of the periciliary liquid in "Cystic Fibrosis" airway disease results in reduced mucociliary transport, persistent mucus hypersecretion and consequently increased height of the luminal mucus layer, so hypoxic gradients in the mucus plugs are developed. Because of anaerobic lung zones, it is highly probable that anaerobic bacteria not detected by routine bacteriologic culture methods also reside within the mucus. Notwithstanding this evidence, microbiology laboratories working in the cystic fibrosis field do not generally use strict anaerobic bacteriologic cultures to determine the presence of anaerobic bacteria in the Cystic Fibrosis lung. The aim of this review is to focus on the published data regarding the finding of anaerobic bacteria in cystic fibrosis airway disease. Therefore, microbiology, diagnosis, antimicrobial susceptibility and possible impact on clinical management of anaerobic bacteria lung infection in cystic fibrosis are described.